This project aims to adapt and miniaturize a previously developed OMA-1 activity assay to 1,536-well format for high-throughput screening. This assay will then be utilized to identify/develop specific OMA1 inhibitors, which have the potential to be used therapeutically in a wide range of disease states. Inhibitor candidates will be tested as therapeutics in renal cell injury models using mitochondrial stressors. During this period, the project team designed and tested different reagents for the OMA1 activity assay to improve signal strength and assay window, in pursuit of making the assay HTS-amenable for intended future screening.